Transcript segment

Baric Transcribed Interview (Redacted), pp.92-94 · baric_ti:utt:00829

Page text: p.92, p.93, p.94 · original PDF

Date: 2026-04-10 09:00 (day precision)
Type: transcript segment · interview
recipient: Christina Salazar, Harry Kazenoff, David T. Lambeth III, William Henderson, Clark Ervin, Jake Greenberg
speaker: Ralph S. Baric
Topics: Furin cleavage site and molecular features Gain-of-function research Vaccines

That's a gain-of-function experiment. There's no other way to think about it. You can do loss18 of-function, but it doesn't prove that it's jumping across there. All you say is you knock that mutation out, it loses the ability. Gain-of-function proves it, and it's causal. So in my opinion, when I read that, that's exactly what they're asking for. They mention in there that this could involve gain-of-function research in their announcement. So part one of that grant was to do surveillance in China, looking in that case for viruses. DC.Scheduling@LexitasLegal.com As part of the thought process, there were two questions. There were two ideas that came forward. One was why don't sarbecoviruses have furin cleavage sites. And I've studied coronaviruses all my life. I know sarbecoviruses. I've seen zoonotic strains. They don't have furin cleavage sites. MERS strains do. Human coronaviruses do. Feline coronaviruses do. Why don't sarbecos? There should be sarbecos out there that have furin cleavage sites, so they were going to look for them. Once they found them and they sequenced it they were going to work on it with pseudotypes. They were going to drop those spike genes into pseudotypes and ask what's -- we were also going to look at the receptor binding domain, obviously, and I think we hypothesized in there that there should be strains with 25 percent variation in spike that could still use the ACE2 receptor. And those are obviously of interest because if you're interested in developing pan18 sarbecovirus vaccines or drugs you want, in essence, the bookends of the heterogeneity that exists in the virus subgenus, right. You want strains that you know and strains that are very different, because you have no idea what would emerge in the future. So if you have breadth then you have a better chance of developing something that could be used immediately. So those are two major features. The first part would DC.Scheduling@LexitasLegal.com be then to find sarbecoviruses. If we found the sarbecovirus with a furin cleavage site it would be dropped into a pseudovirus, and its biological characteristics evaluated by the Chinese. They would remove the furin cleavage site. They would introduce changes into the receptor binding domain and look in the context of those pseudotypes, which is the safe system, to ask questions about what the role of those mutations were in tropism and entry of viruses in receptor usage. Following gleaning that data, we would then use a zoonotic sarbecovirus as a receptacle to drop the spike genes of some of these viruses, and if we found one with full-on furin site we would put it in there and evaluate its biology. We would also remove that furin cleavage site and ask what the effect was on pathogenesis in replication. So it's a loss-of-function first. At the end of that there was speculation that if the furin cleavage site looked like it was having effect on replication of pathogenesis we would consider putting it into a gain-of-function scenario where we would drop it into a null backbone. So that's how the experiment was written.

Extracted statements

Rule-extracted, not adjudicated. The grade says what may be done with each one; read the document above before relying on any of them.

Statement	Grade	Attribution	Stance
They mention in there that this could involve gain-of-function research in their announcement.	own voice, substantive	speaker_own	asserts
One was why don't sarbecoviruses have furin cleavage sites.	needs context	speaker_own	asserts
There should be sarbecos out there that have furin cleavage sites, so they were going to look for them.	own voice, substantive	speaker_own	asserts
They were going to drop those spike genes into pseudotypes and ask what's -- we were also going to look at the receptor binding domain, obviously, and I think we hypothesized in there that there should be strains with 25 percent variation in spike that could still use the ACE2 receptor.	needs context	uncertain explicit hedge	asserts
If we found the sarbecovirus with a furin cleavage site it would be dropped into a pseudovirus, and its biological characteristics evaluated by the Chinese.	quoted / not their view	hypothetical conditional framing	asserts
They would remove the furin cleavage site.	needs context	speaker_own	asserts
They would introduce changes into the receptor binding domain and look in the context of those pseudotypes, which is the safe system, to ask questions about what the role of those mutations were in tropism and entry of viruses in receptor usage.	own voice, substantive	speaker_own	asserts
Following gleaning that data, we would then use a zoonotic sarbecovirus as a receptacle to drop the spike genes of some of these viruses, and if we found one with full-on furin site we would put it in there and evaluate its biology.	own voice, substantive	speaker_own	asserts
We would also remove that furin cleavage site and ask what the effect was on pathogenesis in replication.	own voice, substantive	speaker_own	asserts
At the end of that there was speculation that if the furin cleavage site looked like it was having effect on replication of pathogenesis we would consider putting it into a gain-of-function scenario where we would drop it into a null backbone.	own voice, substantive	speaker_own	asserts

Statement

Grade

Attribution

Stance

They mention in there that this could involve gain-of-function research in their announcement.

own voice, substantive

speaker_own

asserts

One was why don't sarbecoviruses have furin cleavage sites.

needs context

speaker_own

asserts

There should be sarbecos out there that have furin cleavage sites, so they were going to look for them.

own voice, substantive

speaker_own

asserts

They were going to drop those spike genes into pseudotypes and ask what's -- we were also going to look at the receptor binding domain, obviously, and I think we hypothesized in there that there should be strains with 25 percent variation in spike that could still use the ACE2 receptor.

needs context

uncertain explicit hedge

asserts

If we found the sarbecovirus with a furin cleavage site it would be dropped into a pseudovirus, and its biological characteristics evaluated by the Chinese.

quoted / not their view

hypothetical conditional framing

asserts

They would remove the furin cleavage site.

needs context

speaker_own

asserts

They would introduce changes into the receptor binding domain and look in the context of those pseudotypes, which is the safe system, to ask questions about what the role of those mutations were in tropism and entry of viruses in receptor usage.

own voice, substantive

speaker_own

asserts

Following gleaning that data, we would then use a zoonotic sarbecovirus as a receptacle to drop the spike genes of some of these viruses, and if we found one with full-on furin site we would put it in there and evaluate its biology.

own voice, substantive

speaker_own

asserts

We would also remove that furin cleavage site and ask what the effect was on pathogenesis in replication.

own voice, substantive

speaker_own

asserts

At the end of that there was speculation that if the furin cleavage site looked like it was having effect on replication of pathogenesis we would consider putting it into a gain-of-function scenario where we would drop it into a null backbone.

own voice, substantive

speaker_own

asserts

In context

A single line often inverts meaning once you see what it answers, so neighbouring messages are always shown.

2026-04-10 09:00 Ralph S. Baric open

Yes.
2026-04-10 09:00 Christina Salazar open

-- that they specifically said "we want you to do gain-of-function research."
2026-04-10 09:00 Ralph S. Baric open

They said they want you to know, down to the nucleotide level what drives cross-species jumping events.
2026-04-10 09:00 Christina Salazar open

And that's gain-of-function research.
2026-04-10 09:00 Ralph S. Baric

That's a gain-of-function experiment. There's no other way to think about it. You can do loss18 of-function, but it doesn't prove that it's jumping across there. All you say is you knock that mutation out, it loses the ability. Gain-of-function proves it, and it's causal. So in my opinion, when I read that, that's exactly what they're asking for. They mention in there that this could involve gain-of-function research in their announcement. So part one of that grant was to do surveillance in China, looking in that case for viruses. DC.Scheduling@LexitasLegal.com As part of the thought process, there were two questions. There were two ideas that came forward. One was why don't sarbecoviruses have furin cleavage sites. And I've studied coronaviruses all my life. I know sarbecoviruses. I've seen zoonotic strains. They don't have furin cleavage sites. MERS strains do. Human coronaviruses do. Feline coronaviruses do. Why don't sarbecos? There should be sarbecos out there that have furin cleavage sites, so they were going to look for them. Once they found them and they sequenced it they were going to work on it with pseudotypes. They were going to drop those spike genes into pseudotypes and ask what's -- we were also going to look at the receptor binding domain, obviously, and I think we hypothesized in there that there should be strains with 25 percent variation in spike that could still use the ACE2 receptor. And those are obviously of interest because if you're interested in developing pan18 sarbecovirus vaccines or drugs you want, in essence, the bookends of the heterogeneity that exists in the virus subgenus, right. You want strains that you know and strains that are very different, because you have no idea what would emerge in the future. So if you have breadth then you have a better chance of developing something that could be used immediately. So those are two major features. The first part would DC.Scheduling@LexitasLegal.com be then to find sarbecoviruses. If we found the sarbecovirus with a furin cleavage site it would be dropped into a pseudovirus, and its biological characteristics evaluated by the Chinese. They would remove the furin cleavage site. They would introduce changes into the receptor binding domain and look in the context of those pseudotypes, which is the safe system, to ask questions about what the role of those mutations were in tropism and entry of viruses in receptor usage. Following gleaning that data, we would then use a zoonotic sarbecovirus as a receptacle to drop the spike genes of some of these viruses, and if we found one with full-on furin site we would put it in there and evaluate its biology. We would also remove that furin cleavage site and ask what the effect was on pathogenesis in replication. So it's a loss-of-function first. At the end of that there was speculation that if the furin cleavage site looked like it was having effect on replication of pathogenesis we would consider putting it into a gain-of-function scenario where we would drop it into a null backbone. So that's how the experiment was written.
2026-04-10 09:00 Christina Salazar open

And who was going to be doing that work?
2026-04-10 09:00 Ralph S. Baric open

That part would be done by me.
2026-04-10 09:00 Christina Salazar open

Okay. DC.Scheduling@LexitasLegal.com
2026-04-10 09:00 Ralph S. Baric open

Well, at least that's the way the grant was written initially. Whether that would have functionally happened is a fair question, because if the Chinese discovered the virus, the question always exists whether they would share it with me to do that work or not.

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